Metabolic and endocrine abnormalities are well-described in HIV- infected men and women. Several findings indicate a possible influence of sex hormone levels on AIDS progression. These include 1) the relationship of deceased serum sex hormone levels to HIV-associated wasting, 2) the possible benefits of testosterone replacement therapy on body composition, 3) the recent observation that men and women have varying levels of HIV- viral loads. The mechanisms of sex hormone deficiency in HIV- infected men and women may relate to the combined effects of chronic illness, under-nutrition and a complex regimen of medications. Injection drug users (IDU), with or without co- existing HIV infection, may be susceptible to similar metabolic abnormalities, however little is known of the hormonal milieu of this cohort in which an estimated 50 percent of new HIV infections occur. Improved understanding of the overall health status of the IDU may enhance the effectiveness of the relative cures already available to the IDU and subsequently increase control of the AIDS epidemic in this cohort. We hypothesize that male and female IDU are predisposed to endocrine abnormalities, such as hypogonadism, which leads to reductions in lean body mass and quality of life (QOL), and that treatment of male hypogonadism with testosterone improves these parameters. Our overall goal is to understand the effects of IDU and HIV on the hormonal milieu. In a population of men and women, stratified by IDU and HIV status, our specific aims are: 1) To document gonadal function, 2) To determine the relationship of sex steroids to body composition, 3) To ascertain a prevalence estimate of the lipodystropy/metabolic syndrome (as defined in the grant), and 4) To evaluate the safety and efficacy of testosterone replacement therapy on QOL and body composition in men, stratified by HIV status, who have agreed to accept methadone treatment. We propose two clinical experiments: Study A is a cross-sectional study of heroin and/or cocaine dependent men and women, stratified by HIV status to evaluate their hormonal milieu and body composition. Study B is a randomized, placebo-controlled, clinical trial in which men with low serum testosterone levels on chronic methadone will be treated with active or placebo testosterone. Our outcome measures are serum hormones, body composition, muscle strength, and QOL. In summary, we intend to characterize the effects of HIV and IDU on the metabolic/endocrine system in men and women and to perform a clinical trial using testosterone replacement therapy in men. These studies can provide information to further our understanding of gender differences in disease progression and treatment.